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Lakartidningen Aug 2020
Topics: Amdinocillin Pivoxil; Humans; Pyelonephritis
PubMed: 32852775
DOI: No ID Found -
Scandinavian Journal of Primary Health... Sep 2020To compare the proportion of therapy failure, recurrence and complications within 30 days after consultation between men diagnosed with lower urinary tract infection...
OBJECTIVE
To compare the proportion of therapy failure, recurrence and complications within 30 days after consultation between men diagnosed with lower urinary tract infection (UTI) treated with narrow-spectrum antibiotics (nitrofurantoin or pivmecillinam) and broad-spectrum antibiotics (fluoroquinolones or trimethoprim or trimethoprim/sulfamethoxazole).
DESIGN
A retrospective cohort study based on data derived from electronic medical records between January 2012 and December 2015.
SETTING
Primary health care and hospital care in five different counties in Sweden. A total of 16,555 men aged between 18 and 79 years diagnosed with lower UTI.
MAIN OUTCOME MEASURES
Treatment with narrow-spectrum antibiotics was compared with broad-spectrum antibiotics regarding therapy failure, recurrence and complications within 30 days.
RESULTS
The median age of included men was 65 IQR (51-72) years. Narrow-spectrum antibiotics were prescribed in 8457 (40%) and broad-spectrum antibiotics in 12,667 (60%) cases, respectively. Therapy failure was registered in 192 (0.9%), recurrence in 1277 (6%) and complications in 121 (0.6%) cases. Therapy failure and recurrence were more common in patients treated with narrow-spectrum antibiotics and trimethoprim ( < 0.001), but no such difference could be detected regarding complications.
CONCLUSION
There was no difference in incidence of complications within 30 days between men treated with narrow- or broad-spectrum antibiotics. Patients prescribed broad-spectrum antibiotics had lower odds of reconsultation because of therapy failure and recurrence. From current data, treatment with narrow-spectrum antibiotics seems to be an optimal choice regarding preventing complications when treating men with lower UTI. KEY POINTS Complications such as pyelonephritis and sepsis are uncommon in men diagnosed with lower urinary tract infection treated with antibiotics. There was no difference in incidence of complications among men diagnosed with lower urinary tract infection treated with narrow- or broad-spectrum antibiotics. In spite of higher incidence of therapy failure and recurrence, treatment with narrow-spectrum antibiotics seems to be an optimal choice regarding preventing complications when treating men diagnosed with lower UTI.
Topics: Adolescent; Adult; Aged; Amdinocillin Pivoxil; Anti-Bacterial Agents; Humans; Male; Middle Aged; Pyelonephritis; Retrospective Studies; Urinary Tract Infections; Young Adult
PubMed: 32686974
DOI: 10.1080/02813432.2020.1794409 -
Infectious Diseases (London, England) Jun 2020There is a lack of evidence on treatment of urinary tract infections (UTIs) in male patients in a primary care setting, and whether narrow-spectrum antibiotics are safe...
There is a lack of evidence on treatment of urinary tract infections (UTIs) in male patients in a primary care setting, and whether narrow-spectrum antibiotics are safe and effective. To explore antibiotic switch rates after treatment with UTI antibiotics in men over the last 11 years. We analysed data from the Norwegian Prescription Database (NorPD). Men ≥16 years receiving cefalexin, ciprofloxacin, cotrimoxazole, nitrofurantoin, ofloxacin, pivmecillinam or trimethoprim during the period 2008-2018 were included. Antibiotic switch was defined as being prescribed a different antibiotic drug appropriate for UTI within 14 days after initial treatment. We calculated rates of antibiotic switch and corresponding odds ratios for each antibiotic drug. Seven hundred twenty-six thousand and ninety-six (726,096) prescriptions to 429,807 men were defined as possible UTI episodes. Fluoroquinolones, pivmecillinam and cotrimoxazole were most frequently prescribed. Forty-nine thousand five hundred and thirty-one (49,531) (6.8%) of the treatments resulted in antibiotic switch. Compared to cotrimoxazole, the risk of antibiotic switch was higher for pivmecillinam (OR: 2.46; 95% CI, 2.39-2.53) and trimethoprim (OR: 2.12; 95% CI, 2.04-2.20), and lower for fluoroquinolones (OR: 0.40; 95% CI, 0.39-0.42) and cefalexin (OR: 0.28; 95% CI, 0.26-0.30). Treatment duration of ≥7 days and age of ≥50 years were associated with an increased risk of antibiotic switch. Fluoroquinolones and cefalexin were associated with lower antibiotic switch rates than the recommended UTI antibiotics (pivmecillinam, nitrofurantoin and trimethoprim). However, the rates of antibiotic switch following treatment of male patients with first-line empirical UTI antibiotics are relatively low, indicating that the current guidelines are safe.
Topics: Amdinocillin Pivoxil; Anti-Bacterial Agents; Cephalexin; Drug Substitution; Fluoroquinolones; Humans; Male; Middle Aged; Nitrofurantoin; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections
PubMed: 32174201
DOI: 10.1080/23744235.2020.1736329 -
Scandinavian Journal of Primary Health... Mar 2020
Topics: Adolescent; Adult; Amdinocillin Pivoxil; Anti-Bacterial Agents; Denmark; Escherichia coli; Humans; Male; Middle Aged; Nitrofurantoin; Prescriptions; Retrospective Studies; Trimethoprim; Urinary Tract Infections; Young Adult
PubMed: 31997687
DOI: 10.1080/02813432.2020.1718301 -
APMIS : Acta Pathologica,... Mar 2020The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community-acquired urinary tract infections (ca-UTIs) caused by...
The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community-acquired urinary tract infections (ca-UTIs) caused by ESBL-producing Escherichia coli. Eighty-nine ESBL-producing E. coli isolated from women suffering from ca-UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip. Whole genome sequencing was performed on a MiSeq platform, and genome assembly was performed using SPAdes v3.11.0. Neither mecillinam MICs nor ESBL genotypes were associated with treatment outcome of patients treated with pivmecillinam. Specific STs, however, showed significant differences in treatment outcome. Patients infected with ST131 were more likely to experience treatment failure compared to patients infected with non-ST131 (p 0.02) when adjusted for pivmecillinam dose, mecillinam MIC and severity of infection. Patients infected with ST69 were more often successfully treated compared to patients infected with non-ST69 (p 0.04). Patients infected with bla ST131 strains were more likely to experience treatment failure than those infected with non-bla ST131 strains (p 0.02). The results suggest that specific STs are associated with the clinical efficacy of pivmecillinam. Further studies with a larger number of strains, including a larger number of mecillinam resistant strains, are needed to confirm these results.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amdinocillin Pivoxil; Anti-Bacterial Agents; Community-Acquired Infections; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Microbial Sensitivity Tests; Middle Aged; Risk Factors; Treatment Failure; Treatment Outcome; Urinary Tract; Urinary Tract Infections; Young Adult; beta-Lactamases
PubMed: 31755584
DOI: 10.1111/apm.13013 -
MicrobiologyOpen Dec 2019Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to...
Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL-producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full-length LPS with O-antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in bla to bla , loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in bla with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first-line treatment for UTI.
Topics: Amdinocillin; Amdinocillin Pivoxil; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Genome, Bacterial; Genomics; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Mutation; Phylogeny; Whole Genome Sequencing; beta-Lactamases
PubMed: 31573735
DOI: 10.1002/mbo3.941 -
EClinicalMedicine Jul 2019To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract...
Three versus five days of pivmecillinam for community-acquired uncomplicated lower urinary tract infection: A randomised, double-blind, placebo-controlled superiority trial.
BACKGROUND
To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract infection (UTI).
METHODS
A randomised, double-blind, placebo-controlled trial conducted at nine primary care centres in Denmark. 368 women (18-70 years) with symptoms compatible with UTI were randomised to blinded therapy of 5 days [5d] or 3 days followed by 2 days of placebo [3d] from May 2015 to November 2017. Clinical data were assessed using a validated questionnaire at inclusion (day-0), daily the following 7 days and once again within the 2nd to 6th week after intervention. Bacteriological data were collected prior to intervention and twice between day 7 and 42. Main clinical endpoints were days to symptom resolution within 7 days after inclusion and proportions with clinical success at the end of intervention. Main bacteriological endpoint was proportion of participants with significant reduction of bacteriuria (≥ 10 CFU/mL) in 1st control urine sample. ClinicalTrialsRegister.eu: 2014-001321-32.
FINDINGS
180 (5d) and 188 (3d) participants were included in the study (mean age: 35.4 [5d] and 34.9 [3d]). Of these, 125 (70% [5d]) and 122 (66% [3d]) had a positive baseline urine culture. Forty-four participants were lost to follow-up, leaving 161 [5d] and 163 [3d] participants for analysis, respectively. Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P = .894). Clinical success at the end of treatment occurred for 117 of 153 (76%) receiving the 5d-course and for 115 of 157 (73%) receiving the 3d course (difference 3.2% [95% CI -7.1% - 13.5%]; P = .601). Bacteriological success was seen in 92 of 104 (88%) participants given the 5d course and in 86 of 99 (87%) given the 3d course (difference 1.6% [95% CI -8.4%-11.6%]; P = .895).
INTERPRETATIONS
A 5-day course of pivmecillinam was not superior to a 3-day course in clinical or bacteriological outcomes for UTI.
PRIMARY FUNDING SOURCE
The Danish Regions [no. 14/217].
PubMed: 31388664
DOI: 10.1016/j.eclinm.2019.06.009 -
The Journal of Urology Oct 2019
Topics: Amdinocillin Pivoxil; Anti-Infective Agents, Urinary; Double-Blind Method; Female; Humans; Ibuprofen; Urinary Tract Infections
PubMed: 31271546
DOI: 10.1097/JU.0000000000000432 -
American Journal of Obstetrics and... Dec 2019Antibiotics are commonly prescribed during pregnancy. Although the safety of most penicillins is well established, some controversy and uncertainty are associated with...
BACKGROUND
Antibiotics are commonly prescribed during pregnancy. Although the safety of most penicillins is well established, some controversy and uncertainty are associated with the use of other commonly prescribed antibiotics.
OBJECTIVE
To determine the risk of congenital malformations following first-trimester in utero exposure to 10 commonly prescribed antibiotics in Denmark.
MATERIALS AND METHODS
This was a cohort study comprising all singleton liveborn children in Denmark between 2000 and 2015. Data on malformations were collected through 2016. Merging validated and comprehensive populationwide Danish healthcare and civic registries, we merged data on pregnancy, prescription drugs purchases during first trimester and congenital malformations. Using logistic regression, we calculated the odds ratio for congenital malformations (any), major congenital malformations, and cardiac congenital malformations for the 10 most commonly prescribed antibiotics (excluding 4 penicillins that served as control). In the primary analysis, the exposed cohort was compared to a cohort exposed to any of 4 penicillins considered safe during pregnancy (ampicillin, pivampicillin, benzylpenicillin, and phenoxymethylpenicillin). In sensitivity analysis, the exposed cohort was compared to an unexposed cohort. Covariate adjustments were made for maternal age at delivery, year of delivery, parity, pre-pregnancy body mass index, smoking, educational status, employment status, and annual personal income.
RESULTS
We found no increased risk of congenital malformations to be related to first-trimester in utero exposure to the 10 most commonly prescribed antibiotics in Denmark compared to a cohort of pregnant women exposed to penicillins that are considered safe during pregnancy. Compared to unexposed pregnancies, small increased risks for major malformations and cardiac malformations were apparent for pivmecillinam (odds ratio, 1.13; confidence interval, 1.06-1.19; and odds ratio, 1.15; confidence interval, 1.04-1.28, respectively), sulfamethizole (odds ratio, 1.15; confidence interval, 1.07-1.24; and odds ratio, 1.22; confidence interval, 1.07-1.39, respectively), and azithromycin (odds ratio, 1.19, confidence interval, 1.03-1.38; and odds ratio, 1.29, confidence interval, 0.99-1.67, respectively).
CONCLUSION
In this large populationwide cohort study, we found, with a high degree of precision, no increased risk of congenital malformations following first-trimester exposure to 10 commonly prescribed systemic antibiotics.
Topics: Adult; Amdinocillin Pivoxil; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Cohort Studies; Congenital Abnormalities; Denmark; Educational Status; Employment; Female; Heart Defects, Congenital; Humans; Logistic Models; Maternal Age; Maternal Exposure; Obesity, Maternal; Odds Ratio; Penicillins; Pregnancy; Pregnancy Trimester, First; Smoking; Sulfamethizole; Young Adult
PubMed: 31260651
DOI: 10.1016/j.ajog.2019.06.050 -
International Journal of Clinical... Sep 2019Extended Spectrum βeta-lactamase (ESBL)-producing Enterobacteriaceae causing urinary tract infections (UTIs) appear resistant to many common oral agents. There is a...
BACKGROUND
Extended Spectrum βeta-lactamase (ESBL)-producing Enterobacteriaceae causing urinary tract infections (UTIs) appear resistant to many common oral agents. There is a growing need to discover new antibiotics to combat with emerging antibiotic resistance problem. Until the discovery of new antimicrobials, we can bring back forgotten antibiotics to our clinical formulary. Pivmecillinam (prodrug of mecillinam), an oral antimicrobial agent is effective against ESBL producing organisms. We analysed the sensitivity rates of ESBL-producing Enterobacteriaceae from urine samples to mecillinam and to document if pivmecillinam is a suitable alternative option in the treatment of UTI.
MATERIALS/METHODS
This retrospective study was conducted from September 2015 to September 2017. Data were collected from the pathology information system. Antimicrobial sensitivity testing on ESBL-producing Enterobacteriaceae isolates was carried out by disc diffusion method in accordance with The European Committee on Antimicrobial Susceptibility Testing.
RESULTS
A total of 986 ESBL-producing Enterobacteriaceae were tested for mecillinam during the study period. Of 986 organisms, Escherichia coli was the most common organism (889); followed by Klebsiella species (71) and others Enterobacteriaceae (26). Mecillinam sensitivity was found in 96% Escherichia coli (855/889 isolates), 83% Klebsiella species (59/71 isolates) and 88% other Enterobacteriaceae (23/26 isolates). Overall 95% (935/986 isolates) of ESBL-producing urinary isolates were sensitive to mecillinam.
CONCLUSIONS
Pivmecillinam appears to be suitable option to treat ESBL-producing Enterobacteriaceae causing uncomplicated UTI. Our results showed low resistance rate to mecillinam. We recommend the use of pivmecillinam in uncomplicated UTIs because of ESBL-producing Enterobacteriaceae. More studies on in vitro activity of mecillinam against ESBL producing organism and its use and clinical outcome should be tried in future.
Topics: Amdinocillin Pivoxil; Anti-Infective Agents, Urinary; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Urinary Tract Infections; beta-Lactamases
PubMed: 31243859
DOI: 10.1111/ijcp.13387